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Fluorescence-mediated Tomography for the Detection and Quantification of Macrophage-related Murine Intestinal Inflammation
Published on: December 15, 2017
PET imaging detection of macrophages with a formyl peptide receptor antagonist
Yi Zhang1, Bijoy Kundu1, Min Zhong1
1Department of Radiology & Medical Imaging, University of Virginia, Charlottesville, VA 22908.
Abstract:
Macrophages are a major inflammatory cell type involved in the development and progression of many important chronic inflammatory diseases. We previously found that apolipoprotein E-deficient (Apoe(-/-)) mice with the C57BL/6 (B6) background develop type 2 diabetes mellitus (T2DM) and accelerated atherosclerosis when fed a Western diet and that there are increased macrophage infiltrations in pancreatic islets and aorta. The formyl peptide receptor 1 (FPR1) is abundantly expressed on the surface of macrophages. The purpose of this study was to evaluate the applicability of cinnamoyl-F-(D)L-F-(D)L-F (cFLFLF), a natural FPR1 antagonist, to detection of macrophages in the pancreatic islets and aorta. (64)Cu labeled cFLFLF and (18)F-fluorodeoxyglucose (FDG) were administered to mice with or without T2DM. Diabetic mice showed an increased (18)FDG uptake in the subcutaneous fat compared with control mice, but pancreatic uptake was minimal for either group. In contrast, diabetic mice exhibited visually noticeable more cFLFLF-(64)Cu retention in pancreas and liver than control mice. The heart and pancreas isolated from diabetic mice contained more macrophages and showed stronger PET signals than those of control mice. Flow cytometry analysis revealed the presence of macrophages but not neutrophils in pancreatic islets. Real-time PCR analysis revealed much higher FPR1 expression in pancreatic islets of diabetic over control mice. Autoradiography and immunohistochemical analysis confirmed abundant FPR1 expression in atherosclerotic lesions. Thus, (64)Cu-labeled cFLFLF peptide is a more effective PET agent for detecting macrophages compared to FDG.
Insights
A novel PET imaging agent, (64)Cu-labeled cFLFLF, effectively detects macrophages in diabetic mice, outperforming FDG for imaging pancreatic islets and atherosclerotic lesions.
Area of Science:
- Biomedical Imaging
- Inflammatory Diseases
- Molecular Imaging
Background:
- Macrophages are key inflammatory cells in chronic diseases like type 2 diabetes mellitus (T2DM) and atherosclerosis.
- Apolipoprotein E-deficient (Apoe(-/-)) mice on a Western diet exhibit T2DM, accelerated atherosclerosis, and increased macrophage infiltration in pancreatic islets and aorta.
- Formyl peptide receptor 1 (FPR1) is highly expressed on macrophages, making it a potential imaging target.
Purpose of the Study:
- To evaluate the efficacy of cinnamoyl-F-(D)L-F-(D)L-F (cFLFLF), a natural FPR1 antagonist, for detecting macrophages in pancreatic islets and aorta.
- To compare the performance of (64)Cu-labeled cFLFLF with (18)F-fluorodeoxyglucose (FDG) for PET imaging of macrophages in a T2DM mouse model.
Main Methods:
- Administration of (64)Cu-labeled cFLFLF and (18)F-FDG to T2DM and control mice.
- Positron Emission Tomography (PET) imaging to assess tracer uptake in various organs.
- Flow cytometry, real-time PCR, autoradiography, and immunohistochemistry to validate macrophage presence and FPR1 expression.
Main Results:
- Diabetic mice showed increased (18)FDG uptake in subcutaneous fat but minimal pancreatic uptake.
- (64)Cu-cFLFLF exhibited higher retention in the pancreas and liver of diabetic mice compared to controls.
- Diabetic mouse hearts and pancreases had more macrophages and stronger PET signals with (64)Cu-cFLFLF; FPR1 expression was significantly higher in pancreatic islets of diabetic mice.
Conclusions:
- (64)Cu-labeled cFLFLF is a promising PET agent for detecting macrophages in T2DM and atherosclerosis.
- This tracer demonstrates superior performance over FDG for visualizing macrophage infiltration in pancreatic islets and atherosclerotic lesions.
